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Blood Test for a Suicide-Risk Gene Proposed

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If it were possible to reliably identify people who have a higher risk of attempting suicide, more suicides could be prevented. While no simple, consistent means of assessing risk currently exists, one may soon be possible, report Johns Hopkins researchers. According to these scientists, alterations to a single gene can help predict suicidal behavior. What’s more, these alterations may be detected via a simple blood test.

A team of researchers led by Zachary Kaminsky, Ph.D., an assistant professor of psychiatry and behavioral sciences at Johns Hopkins, scrutinized genes for epigenetic variation that might be associated with suicide and suicidal behaviors. Their investigation led them to SKA2, a gene that is involved in brain’s response to stress hormones. Additive genetic and epigenetic changes to this gene appear to play a significant role in turning what might otherwise be an unremarkable reaction to the strain of everyday life into suicidal thoughts and behaviors.

This finding appeared July 30 in the American Journal of Psychiatry, in an article entitled, “Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors.” The article detailed how the investigators employed genome-wide DNA methylation profiling on neuronal and glial nuclei in a discovery set of postmortem brains.

“SKA2 gene expression was significantly lower in suicide decedents and was associated with genetic and epigenetic variation of rs7208505, possibly mediated by interaction with an intronic microRNA, miR-301a,” wrote the authors. “Analysis of salivary cortisol measurements suggested that SKA2 epigenetic and genetic variation may modulate cortisol suppression, consistent with its implicated role in glucocorticoid receptor transactivation.”

The researchers also tested three different sets of blood samples, the largest one involving 325 participants. They found similar methylation increases at SKA2 in individuals with suicidal thoughts or attempts. They then designed a model analysis that predicted which of the participants were experiencing suicidal thoughts or had attempted suicide with 80% certainty. Those with more severe risk of suicide were predicted with 90% accuracy. In the youngest dataset, they were able to identify with 96% accuracy whether or not a participant had attempted suicide, based on blood test results.

The SKA2 gene is expressed in the prefrontal cortex of the brain, which is involved in inhibiting negative thoughts and controlling impulsive behavior. SKA2 is specifically responsible for chaperoning stress hormone receptors into cells’ nuclei so they can do their job. If there isn’t enough SKA2, or it is altered in some way, the stress hormone receptor is unable to suppress the release of cortisol throughout the brain. Previous research has shown that such cortisol release is abnormal in people who attempt or die by suicide.

Dr. Kaminsky said that a test based on these findings might best be used to predict future suicide attempts in those who are ill, to restrict lethal means or methods among those at risk, or to make decisions regarding the intensity of intervention approaches. He added that it might make sense for use in the military to test whether members have the gene mutation that makes them more vulnerable. Those at risk could be more closely monitored when they returned home after deployment. A test could also be useful in a psychiatric emergency room as part of a suicide risk assessment when doctors try to assess level of suicide risk.

"We have found a gene that we think could be really important for consistently identifying a range of behaviors from suicidal thoughts to attempts to completions," Dr. Kaminsky says. "We need to study this in a larger sample but we believe that we might be able to monitor the blood to identify those at risk of suicide."

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